The aim of this program project is to study the basic mechanisms of red cell and hemoglobin behavior underlying the disease state etiology of the red cell. In vitro studies of the more clinically oriented workers cover the effect of antisickling agents on red cells, problems with malaria parasites, effects of high altitude and fetal oxygen delivery. Studies of red cell structure are comprised of EM studies and chemical studies of red cell membrane constituents. The workers on the more basic side study the rheology of red cells in microcirculation, models for sickling reactions in mixed solvent systems, linkage between precipitation of hemoglobin and ligand binding, rheology and low angle alpha-ray scattering of hemoglobin gels, vibrational dichroism of heme-ligand systems, the role of water in regulation of hemoglobin conformation and the thermodynamic balance sheet of linked reaction of hemoglobin.